Effects of Norepinephrine and Phentolamine on Frog Gastric Mucosa in Chloride Solutions

Abstract

In a review article, Holton (1) pointed out that a-agonists, as exemplified by norepinephrine, decrease acid gastric secretion and that this decrease is possibly secondary to vasoconstriction. The isolated frog gastric mucosa provides the opportunity to examine various catecholamines in the absence of vascular effects. Somewhat earlier than the article by Holton, Thorpe et al.(2) investigated the effect of catecholamines on the H+ secretory rate of the isolated bullfrog gastric mucosa. They found that epinephrine and norepinephrine in concentrations as high as 5 x M produced statistically insignificant decreases in histamine-stimulated acid secretion presumably because of the limited number of experiments. However, 5 X lop3 M isoproterenol, a p-agonist , produced significant inhibition of both histamine and acetylcholine-s t im ula t e d H+ secret ion, namely decreases of 55 and 60%, respectively, in the H+ secretory rates. This inhibitory effect of isoproterenol was blocked by propranolol, a p-antagonist. The authors interpreted their data to suggest that isoproterenol inhibits histamine-and acetylcholine-stimulated acid secretion by direct activation of mucosal p-adrenergic receptors. Recent work in our laboratory (3) lends support to this phase of their work.It is evident that Thorpe et al.(2) had limited interest in a-adrenergic amines and that they did not measure the transmucosal resistance and the transmucosal potential difference (PD) concomitantly with the H+ secretory rate. It therefore seemed of interest to study the a-adrenergic amines in greater detail. In this paper, the electrophysiological effects of the adrenergic amines , namely norepinephrine (Levophed), an a-agonist , and phentol-Send reprint requests to amine (Regitine), an a-antagonist , are reported.Methods. The experiments were performed on gastric mucosae of Rana pipiens with an in vitro method described in detail elsewhere (4). Two pairs of electrodes were used, one for sending current across the mucosa and the other for measuring the PD. The resistance was obtained as the change in PD per unit of applied current. The H+ secretory rate was determined by the pH stat method introduced by Durbin and Heinz (5). The pH of the secretory side was maintained at 4.90. The nutrient bathing solution contained (in mM): Na+, 102; K+, 4; Ca2+, 1; Mg2+, 0.8; C1-, 81; HCO,, 25; phosphate, 1.0; and glucose, 10; and the secretory bathing solution contained: Na+, 102; K+, 4; C1-, 106. Both sides of the mucosa were gassed with 95% 0, and 5% CO,. Histamine was added to the nutrient solution to a concentration of M , thereby providing maximal stimulation of the gastric mucosa. After the control part of the experiment, norepinephrine or phentolamine was added in concentrations varying from lod5 to 2 or 2.35 mM. Combinations of these amines were also investigated.Results. Figure 1 shows the effects of adding 1 mM norepinephrine to the nutrient solution. At the time indicated by the first arrow, norepinephrine was added to a concentration of 1 mM in the nutrient...